DESCRIPTION (Applicant's Description) Patients with advanced refractory epithelial ovarian cancer (EOC) have a dismal prognosis, and these patients are left with few therapeutic alternatives with very limited success and/or high morbidity and mortality. EOC is known to produce carcinoembryonic antigen (CEA). Using radio iodinated anti-CEA antibodies, most notably, MN-14 high-affinity anti-CEA MAb, we have also shown excellent targeting of primary and metastatic disease sites in EOC patients. Moreover, anti-tumor effects, including one complete remission and one mixed response, have been achieved with non-myeloablative doses of 131I-MN-14 in 14 evaluable patients who filed conventional chemotherapy. One obstacle in the way of achieving better anti-tumor effects is the advanced bulky disease in most of these patients. The bulky or large volume disease limited the amount of radio labeled MAb uptake, and, hence, the radiation dose delivered to these tumors. We hypothesized that these anti-tumor responses can be largely amplified if substantially (several-fold) higher doses of radioactivity are given. According to the organ and tumor dosimetry studies derived in our clinical experience with 131I-MN-14 in EOC patients, significant tumor radiation doses (i.e., >4000 cGy), and, hence, a higher probability of anti-tumor responses, may be possible with higher doses of 131I-MN-14 (high-dose RAIT). Although the level of radioactivity required to reach these levels will be higher than that tolerated by the hematopoietic system, it is anticipated that other organ systems will be able to tolerate these higher doses. In this proposal, we plan to conduct a phase I, dose escalating trial to determine the maximum tolerated dose (MTD) of the CDR-grafted (humanized) 131I-labeled MN-14 anti-CEA MAb in combination with peripheral blood stem cell rescue (PBSCR) in patients with advanced refractory EOC. Even though this is a phase I trial, there are exciting prospects of significant anti-tumor responses in the participating patients. The development of high-dose radioimmunotherapy in patients with advanced refractory EOC as an effective, yet far less toxic therapeutic modality, may have a significant impact on survival of these unfortunate patients.